Hypertrophic cardiomyopathy (HCM) is a congenital or acquired disorder characterized by marked ventricular hypertrophy with diastolic dysfunction but without increased afterload (eg, from valvular aortic stenosis, coarctation of the aorta, systemic hypertension). Symptoms include dyspnea, chest pain, syncope, and sudden death. A systolic murmur, increased by Valsalva maneuver, is typically present in the hypertrophic obstructive type. Diagnosis is by echocardiography or MRI. Treatment is with β-blockers, verapamil, disopyramide, and sometimes chemical reduction or surgical removal of outflow tract obstruction.

HCM is a common cause of sudden death in young athletes (see Sudden Cardiac Death in Athletes ). It may cause unexplained syncope and may not be diagnosed before autopsy.

Etiology

Most cases of HCM are inherited. At least 50 different mutations that are inherited in an autosomally dominant pattern have been identified; spontaneous mutations are common. Perhaps 1 in 500 people is affected; phenotypic expression varies markedly.

Rarely HCM is acquired. It may develop in patients with acromegaly, pheochromocytoma, and neurofibromatosis.

Pathophysiology

The myocardium is abnormal with cellular and myofibrillar disarray, although this finding is not specific for HCM.

In the most common form, the upper interventricular septum below the aortic valve is markedly hypertrophied and thickened, with little or no hypertrophy of the left ventricular (LV) posterior wall; this pattern is called asymmetric septal hypertrophy and appears to accelerate during puberty. During systole, the septum thickens, and sometimes the anterior leaflet of the mitral valve, already abnormally oriented because of the abnormally shaped ventricle, is sucked toward the septum by a Venturi effect of high velocity blood flow, further obstructing the outflow tract and decreasing cardiac output. The resulting disorder may be termed hypertrophic obstructive cardiomyopathy. Less commonly, midventricular hypertrophy leads to an intracavitary gradient at the papillary muscle level. In both forms, the distal LV may ultimately thin and dilate. Apical hypertrophy can also occur but does not obstruct outflow, although it may obliterate the apical portion of the LV during systole. Sometimes the hypertrophy is diffuse and symmetrical.

Contractility is grossly normal, resulting in a normal ejection fraction (EF). Later, EF is elevated because the ventricle has a small volume and empties nearly completely to maintain cardiac output.

Hypertrophy results in a stiff, noncompliant chamber (usually the LV) that resists diastolic filling, elevating end-diastolic pressure and thus increasing pulmonary venous pressure. As resistance to filling increases, cardiac output decreases, an effect worsened by any outflow tract gradient present. Because tachycardia allows less time for filling, symptoms tend to appear mainly during exercise or tachyarrhythmias.

Infective endocarditis can complicate HCM because of the mitral valve abnormality and because of rapid blood flow through the outflow tract during early systole. Atrioventricular block is sometimes a late complication.

Syncope usually occurs without warning during exertion either because outflow obstruction worsens with the increased contractility or because of nonsustained ventricular or atrial arrhythmia.
Syncope is a marker of increased risk of sudden death, which is thought to result from ventricular tachycardia or fibrillation.

BP and heart rate are usually normal, and signs of increased venous pressure are rare. When the outflow tract is obstructed, the carotid pulse has a brisk upstroke, bifid peak, and rapid downstroke. The apex beat may have a sustained thrust due to LV hypertrophy. A 4th heart sound (S4) is often present and is associated with a forceful atrial contraction against a poorly compliant LV in late diastole.

Septal hypertrophy produces a systolic ejection-type murmur that does not radiate to the neck and may be heard at the left sternal edge in the 3rd or 4th intercostal space. A mitral regurgitation murmur due to distortion of the mitral apparatus may be heard at the apex. When the right ventricular outflow tract is narrowed, a systolic ejection murmur is sometimes heard in the 2nd interspace at the left sternal border. The LV outflow ejection murmur of HCM can be increased by a Valsalva maneuver (which reduces venous return and LV diastolic volume), by measures to lower aortic pressure (eg, nitroglycerin), or by a postextrasystolic contraction (which increases the outflow tract pressure gradient). Handgrip increases aortic pressure, thereby reducing the murmur’s intensity.

Diagnosis

Clinical suspicion (syncope and murmur)

Echocardiography and/or MRI

Diagnosis is suspected based on a typical murmur and symptoms. Suspicion is increased if the patient has a history of unexplained syncope or a family history of unexplained sudden death. Unexplained syncope in young athletes should always raise suspicion. HCM must be distinguished from aortic stenosis and CAD, which cause similar symptoms. ECG and 2-dimensional echocardiography and/or MRI (the best noninvasive confirmatory tests) are done. Chest x-ray is often done but is usually normal because the ventricles are not dilated (although the left atrium may be enlarged). Patients with syncope or sustained arrhythmias should be evaluated as inpatients. Exercise testing and 24-h ambulatory monitoring may be helpful for patients considered at high risk, although accurately identifying such patients is difficult.

The ECG usually shows voltage criteria for LV hypertrophy (eg, S wave in lead V1 plus R wave in lead V5 or V6 > 35 mm). Very deep septal Q waves in leads I, aVL, V5, and V6 are often present with asymmetric septal hypertrophy; HCM sometimes produces a QRS complex in V1 and V2, simulating previous septal infarction. T waves are usually abnormal; the most common finding is deep symmetric T-wave inversion in leads I, aVL, V5, and V6. ST-segment depression in the same leads is common (particularly in the apical obliterative form). The P wave is often broad and notched in leads II, III, and aVF, with a biphasic P wave in leads V1 and V2, indicating left atrial hypertrophy. Incidence of preexcitation phenomenon of the Wolff-Parkinson-White syndrome type, which may cause palpitations, is increased. Bundle branch block is common.

Two-dimensional Doppler echocardiography can differentiate the forms of cardiomyopathy (see see Figure: Forms of cardiomyopathy.) and quantify the degree of outflow tract obstruction, including pressure gradient and area of the stenotic segment. These measurements are particularly useful for monitoring the effect of medical or surgical treatment. Midsystolic closure of the aortic valve sometimes occurs when outflow tract obstruction is severe.

Cardiac catheterization is usually done only when invasive therapy is considered. Usually, no significant stenoses are present in the coronary arteries, but elderly patients may have coexisting CAD. Genetic markers may also be useful to confirm a specific diagnosis.

Prognosis

Overall, annual mortality is 1 to 3% for adults but is higher for children. Mortality rate is inversely proportional to the age at which symptoms appear and is highest in patients who have frequent nonsustained ventricular tachycardia or syncope or have been resuscitated after sudden cardiac arrest. Prognosis is worse for young patients with a family history of sudden death and for patients > 45 yr with angina or exertional dyspnea. Death is usually sudden, and sudden death is the most common sequelae; chronic heart failure occurs less often.

If syncope or sudden cardiac arrest has occurred or if ventricular arrhythmia is confirmed by ECG or 24-h ambulatory monitoring, an implantable cardioverter-defibrillator or antiarrhythmics should be considered. Competitive sports should be avoided because many sudden deaths occur during increased exertion.

Treatment of the dilated congestive phase of HCM is the same as that of dilated cardiomyopathy with predominant systolic dysfunction.

If septal hypertrophy and outflow tract obstruction cause significant symptoms despite medical therapy, surgery is needed. Catheter alcohol ablation is variably effective but is becoming more widely used; surgical septal myotomy or myomectomy reduces symptoms more reliably but may not prolong life.

Genetic counseling is appropriate for patients with asymmetric septal hypertrophy.

Key Points

Hypertrophic cardiomyopathy is usually due to one of numerous genetic mutations that cause various types of ventricular hypertrophy that restrict filling (ie, cause diastolic dysfunction) and sometimes obstruct LV outflow.

Coronary blood flow may be impaired even in the absence of coronary artery atherosclerosis because capillary density is inadequate and the intramyocardial coronary arteries are narrowed by intimal and medial hyperplasia and hypertrophy

At a young age, patients may have chest pain, dyspnea, palpitations, syncope, and sometimes sudden death, typically triggered by exertion.

Echocardiography is done, but, if available, MRI best shows the abnormal myocardium.

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